Overeating May Blunt Brain-Reward Circuitry

Obesity is associated with a reduced ability to feel “rewarded” by food, especially in people whose reduced sense of reward stems from a particular gene variant, according to a study published Oct. 17 in the journal Science.

Although the detailed findings of the study hint at a complex process not yet fully understood, they also suggest that moderately unhealthy behaviors such as overeating can easily run to extremes in the same ways that are seen in drug addiction.

“This is a very nice study, a real contribution,” says Kent Berridge, a neuroscientist at the University of Michigan who has done research in this area.

Two sets of volunteers—43 college-age women and 33 adolescent girls—sipped a chocolate milkshake or a tasteless solution while a functional magnetic resonance imaging (fMRI) machine recorded their brain reactions in the study, performed by Eric Stice, a psychologist at the Oregon Research Institute and the University of Texas at Austin, and colleagues.

The researchers focused on fMRI responses in the dorsal striatum, a key region in the brain’s reward circuitry. Previous studies have found that dopamine activity in this region rises when a person tastes food, and does so more strongly when their self-described sense of enjoyment is higher. Scientists in this field think that such rises in dopamine activity show up as increased fMRI responses.

Stice and his colleagues found that those subjects with higher body mass indexes (BMIs) tended to show weaker fMRI responses to the milkshake compared with the tasteless solution, suggesting that their striatal dopamine responses—and thus their enjoyment of the taste—was weaker.

This association between greater obesity and less enjoyment was even stronger among women who had a specific gene variant believed to reduce the number of relevant dopamine receptors in the striatum.

A complicated picture

Previous studies had strongly suggested a link between obesity and reduced activity in the dorsal striatum.

“Now the finding is moderated by the genetic risk, which lines up perfectly,” says Stice. “So if you’re obese and you have a blunted response in this dopamine-based brain region, and you have a [gene variant] associated with a compromised dopamine signaling, it gives you an amplification of that same blunting response.”

On the other hand, “exactly how it unfolds in real time is not something we’ve figured out yet,” he says. There appear to be many complicating factors.

The researchers followed some of the women for a year after their fMRI scans to find out whether those with a reduced striatal response tended to gain more weight. That turned out to be so only for the women with the gene variant. For the others, those with a reduced striatal response tended to gain less weight.

The study, by design, also wasn’t able to determine whether a reduced striatal response causes obesity, or vice versa. Stice thinks that both are involved, in a vicious spiral: “I strongly suspect it’s a trap you get into, so the more you overeat these unhealthy, high-sugar foods, the more you see a reward dampening, and then you overcompensate by overeating.”

As Berridge notes, it may seem puzzling that a dampening of the enjoyment of food would make a person eat more of it. If people eat more food despite liking it less, it suggests that they also want it more despite liking it less. Berridge and others have argued that wanting and liking are associated with distinct processes in the brain and don’t always go together.

Stice sees a parallel with drug and alcohol abuse, in which users grow dependent not on taste but on other neurochemical effects.

“It’s probably similar to what we know about low-tar cigarettes,” he says. Such cigarettes contain less nicotine, and studies have suggested that smokers unconsciously tend to make up some of that nicotine deficit, for example by inhaling more deeply and by smoking each cigarette a bit longer.

Stice also notes that he and his colleagues have conducted another study, not yet published, showing that obese people have a greater responsiveness when it comes to the anticipation of food-related rewards: “When you tell [obese] people they’re about to get a milkshake, when you even show them pictures of people eating food, in the brain scanner they show greater activation of the reward circuitry.”

Stice says that most areas of the reward circuitry outside the dorsal striatum show greater activation in people who are obese or will have higher weight gain. In other words, much more work needs to be done to determine what dopamine activity really means in different parts of the brain’s reward circuitry. “Another shoe has to drop,” Berridge says.

Still, to Stice, whose research focus is on obesity treatment, it is already clear that obesity can reflect an addiction-like attachment to food that can be hard to break.

“Getting people out of obesity once they’re there is amazingly hard, which is one of the reasons I think prevention is a much more likely scenario in terms of reducing the prevalence of obesity in America,” he says.